John Stephen Dumler
EducationBS Medical Technology - 1978 University of Maryland at Baltimore, Sch Medicine
MD - 1985 University of Maryland at Baltimore, Sch Medicine
POST GRADUATE EDUCATION AND TRAINING:
Anatomic Pathology Residency 1985-1988 Johns Hopkins University School of Medicine
Laboratory Medicine Residency 1988-1989 Johns Hopkins University School of Medicine
Pathology Residency (Research) 1990 University of Texas Medical Branch, Galveston
Postdoctoral Fellowship 1990-1992 University of Texas Medical Branch, Galveston
BiographyResearch Description: The laboratory is predominantly set to investigate vector-borne disease pathogenesis, with a strong emphasis on tick-borne infectious agents and intracellular bacteria in the order Rickettsiales. We employ multidisciplinary approaches toward scientific investigation ranging from simple diagnostic methods for clinical purposes, to molecular, genomic and epigenetic approaches for fundamental scientific discovery. Most basic work focuses on Anaplasma phagocytophilum AnkA, a type IV secretion system substrate that regulates host chromatin and nuclear structure by epigenetic mechanisms to influence eukaryotic gene transcriptional programs by binding gene promoters in cis and by binding chromatin into the nuclear lamina in trans. Additional investigations in the lab focus on i) Rickettsia, Anaplasma, Ehrlichia, and Borrelia infections and immunopathology mediated by NKT and cytotoxic T cells; ii) A. phagocytophilum immunopathology related to NKT, NK, and CD8 T cells immune responses; iii) Stat1 signaling and its role in immunopathology with A. phagocytophilum infection; iv) fundamental mechanisms of vascular permeability with rickettsial infections and pharmacologic interventions; v) 3D microvascular tissue models for investigation of tick-borne pathogen intravasation into the bloodstream and extravasation into tissues; vi) mechanisms of microvascular endothelial barrier activation with SARS-CoV-2 spike proteins and its role in thrombosis and long COVID. We also study tick-borne co-infections and their synergistic pathogenetic mechanisms with Lyme disease and human granulocytic anaplasmosis. Because an underlying tenet of infection pathogenesis with many vector-borne pathogens is increased vascular permeability or access to the vasculature for systemic dissemination, pathogen endothelial cell barrier intravasation, invasion, dissemination, extravasation, and vascular permeability by Borrelia, Rickettsia, Anaplasma, Ehrlichia and other pathogens in vitro and in vivo are significant interests. These studies focus in part on the roles of intracellular calcium concentrations, divalent cation chelators, phospholipase C inhibitors and antagonists of signaling through G protein-coupled receptors that prevent increases in vascular barrier permeability, and on the role that calcium channels and their pharmacologic blockers play. To further these goals, we have established 3 dimensional models of human microvasculature under flow to mimic in vivo blood vessels that will help define pathogen interactions and outcomes in a human model system and reduce dependency on animal models. Finally, the laboratory supports clinical investigations of febrile disease etiology in under-resourced regions, including Malaysia, Sri Lanka, Nicaragua, Uganda, and Tanzania, among other locations, and the incidence and prevalence of other tick-borne infections (e.g. Borrelia) in active duty forces. These studies focus on high-throughput and multiplexed methods for molecular diagnosis and avoidance of misdiagnosis to prevent inappropriate treatment and the consequent negative outcomes. The aims are to i) answer how much fever/disease in such regions is the result of undiagnosed rickettsial or tick-borne disease, and ii) implement clinical studies and trials of new diagnostic tests, therapies and vaccines to prevent these vector-borne infections.
Representative publications, projects, and/or deployments
1992-1995 Assistant Professor, Pathology, University of Maryland School of Medicine
1996-2003 Associate Professor, Department of Pathology, The Johns Hopkins University School of Medicine and Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School Public Health
2003-2013 Professor (tenured 2003), Department of Pathology, The Johns Hopkins University School of Medicine; Department of Molecular Microbiology and Immunology, The Johns Hopkins University Bloomberg School of Hygiene and Public Health
2011-2012 Professor, Pathology and Microbiology, Perdana University Graduate School of Medicine, Serdang, Selangor, Malaysia
2013-2016 Professor, Departments of Pathology and Microbiology & Immunology; University of Maryland School of Medicine.
2016-present Chair, Joint Departments of Pathology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD and Joint Pathology Center, Silver Spring, MD
2010 American Society for Microbiology Becton Dickinson Award for Research in Clinical Microbiology, 110th ASM General Meeting, San Diego, CA
2013 Brindley Visiting Professor, University of Texas Medical Branch, Department of Pathology, Galveston, TX
2013 Meeting Keynote Lecturer, XVII Congreso Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica (Spanish Society of Infectious Diseases and Clinical Microbiology), Zaragoza, Spain; May 29-31, 2013.
2013 Barnett L. Cohen Award, In recognition of contributions, devotion and interest in promoting the science of microbiology; Maryland Branch, American Society for Microbiology; December 4, 2013.
Bakken JS, Dumler JS, Chen SM, Eckman MR, Van Etta LL, Walker DH. Human granulocytic ehrlichiosis in the upper midwest United States. A new species emerging? JAMA 1994;272:212-218.
Goodman JL, Nelson C, Vitale B, Madigan JE, Dumler JS, Kurtti TJ, Munderloh UK. Direct cultivation of the causative agent from patients with human granulocytic ehrlichiosis. N Engl J Med 1996;334:209-215. PMID:8531996
Dumler JS, Barbet AF, Bekker CPJ, Dasch GA, Palmer GH, Ray SC, Rikihisa Y, Rurangirwa FR. Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales; unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia, and Ehrlichia with Neorickettsia; descriptions of six new species combinations; and designation of Ehrlichia equi and "HGE agent” as subjective synonyms of Ehrlichia phagocytophila. Int J Syst Evol Microbiol 2001; 51:2145-2165.
Martin ME, Caspersen K, Dumler JS. Immunopathology and ehrlichial propagation are regulated by interferon gamma (IFN) and interleukin-10 (IL-10) in a murine model of human granulocytic ehrlichiosis (HGE). Am J Pathol 2001, 158:1881-1888.
Dumler JS, Barat NC, Barat CE, Bakken JS. Human granulocytic anaplasmosis and macrophage activation. Clin Infect Dis 2007; 45: 199-204.
Choi KS, Scorpio DG, Dumler JS. Stat1 negatively regulates immune-mediated injury with Anaplasma phagocytophilum infection. J Immunol 2014; 193:5088-98. PMC4225178
Garcia-Garcia JC, Rennoll-Bankert KE, Pelly S, Milstone AM, Dumler JS. Silencing of host cell CYBB Gene expression by the nuclear effector AnkA of the intracellular pathogen Anaplasma phagocytophilum. Infect Immun. 2009; 77:2385-91. PMC2687357.
Garcia-Garcia JC, Barat NC, Trembley SJ, Dumler JS. Epigenetic silencing of host cell defense genes enhances intracellular survival of the rickettsial pathogen Anaplasma phagocytophilum. PLoS Pathogen 2009; 5:e1000488. PMC2694362.
Sinclair SHG, Yegnasubramanian S, Dumler JS. Global DNA methylation changes and differential gene expression in Anaplasma phagocytophilum-infected human neutrophils. Clin Epigenetics 2015 7:77. PMC4518890
Rennoll-Bankert KE, Garcia-Garcia JC, Sinclair SH, Dumler JS. Chromatin-bound bacterial effector ankyrin A recruits histone deacetylase 1 and modifies host gene expression. Cell Microbiol. 2015; 17:1640-1652; PMID: 25996657